Interdependence of PRC1 and PRC2 for recruitment to Polycomb Response Elements

Kahn, Tatyana G.; Dorafshan, Eshagh; Schultheis, Dorothea; Zare, Aman; Stenberg, Per; Reim, Ingolf; Pirrotta, Vincenzo; Schwartz, Yuri B.

doi:10.1093/nar/gkw701

Cited by 89 publications

(133 citation statements)

References 86 publications

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“…According to the more recent extension of this model RYBP containing complexes are targeted first and the effective H2A mono-ubiqitilation drives PRC2 recruitment and consequent Polycomb domain formation in mammals [124]. In Su(z)12 mutant background, H3K27 methylation is nearly completely abolished, but PRC1 targeting remains intact in Drosophila, which is in accordance with the newest model [219].…”

Section: General Description Of Mammalian Ncprc1ssupporting

confidence: 67%

“…They found that RYBP-RING containing variant PRC1 complexes targeted normally in the EED mutant, despite the almost complete loss of PRC2 dependent H3K27 trimethylation. Similarly, in Drosophila, in Su(z)12 mutant background, H3K27 methylation is nearly completely abolished, but PRC1 targeting remains intact [219]. At the same time, these experiments underlined the collateral importance of additional targeting subunits in effective ubiquitination activity of ncPRC1 complexes.…”

Section: Targeting Of Different Ncprc1 Complexesmentioning

confidence: 73%

“…It seems that the order of recruitment can be reversed. In some cases, H3K27 trimethylation independent targeting of ncPRC1 complexes can precede that of PRC2 complexes [219]. According to the more recent extension of this model RYBP containing complexes are targeted first and the effective H2A mono-ubiqitilation drives PRC2 recruitment and consequent Polycomb domain formation in mammals [124].…”

Section: General Description Of Mammalian Ncprc1smentioning

confidence: 99%

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From Flies to Mice: The Emerging Role of Non-Canonical PRC1 Members in Mammalian Development

2018

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Originally two types of Polycomb Repressive Complexes (PRCs) were described, canonical PRC1 (cPRC1) and PRC2. Recently, a versatile set of complexes were identified and brought up several dilemmas in PRC mediated repression. These new class of complexes were named as non-canonical PRC1s (ncPRC1s). Both cPRC1s and ncPRC1s contain Ring finger protein (RING1, RNF2) and Polycomb group ring finger catalytic (PCGF) core, but in ncPRCs, RING and YY1 binding protein (RYBP), or YY1 associated factor 2 (YAF2), replaces the Chromobox (CBX) and Polyhomeotic (PHC) subunits found in cPRC1s. Additionally, ncPRC1 subunits can associate with versatile accessory proteins, which determine their functional specificity. Homozygous null mutations of the ncPRC members in mice are often lethal or cause infertility, which underlines their essential functions in mammalian development. In this review, we summarize the mouse knockout phenotypes of subunits of the six major ncPRCs. We highlight several aspects of their discovery from fly to mice and emerging role in target recognition, embryogenesis and cell-fate decision making. We gathered data from stem cell mediated in vitro differentiation assays and genetically engineered mouse models. Accumulating evidence suggests that ncPRC1s play profound role in mammalian embryogenesis by regulating gene expression during lineage specification of pluripotent stem cells.

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Section: General Description Of Mammalian Ncprc1ssupporting

confidence: 67%

Section: Targeting Of Different Ncprc1 Complexesmentioning

confidence: 73%

Section: General Description Of Mammalian Ncprc1smentioning

confidence: 99%

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From Flies to Mice: The Emerging Role of Non-Canonical PRC1 Members in Mammalian Development

2018

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“…NO, on larval polytene chromosomes [155] Su(z)12 (PRC2) NO, in Drosophila cells [159]. Not reported.…”

Section: Psc and Its Homologue Suppressor Of Zeste 2 (Su(z)2)mentioning

confidence: 98%

“…-PARTIAL: in Drosophila cells [159] E(z) (PRC2) NO, at the bxdPRE in Drosophila cells and larvae [117,158].…”

Section: Psc and Its Homologue Suppressor Of Zeste 2 (Su(z)2)mentioning

confidence: 99%

Drosophila DNA-Binding Proteins in Polycomb Repression

2018

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Abstract:The formation of individual gene expression patterns in different cell types is required during differentiation and development of multicellular organisms. Polycomb group (PcG) proteins are key epigenetic regulators responsible for gene repression, and dysregulation of their activities leads to developmental abnormalities and diseases. PcG proteins were first identified in Drosophila, which still remains the most convenient system for studying PcG-dependent repression. In the Drosophila genome, these proteins bind to DNA regions called Polycomb response elements (PREs). A major role in the recruitment of PcG proteins to PREs is played by DNA-binding factors, several of which have been characterized in detail. However, current knowledge is insufficient for comprehensively describing the mechanism of this process. In this review, we summarize and discuss the available data on the role of DNA-binding proteins in PcG recruitment to chromatin.

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Potential of enhancer of zeste homolog 2 inhibitors for the treatment of SWI/SNF mutant cancers and tumor microenvironment modulation

Pyziak

Sroka-Porada²,

Rzymski³

et al. 2021

Drug Development Research

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Enhancer of zeste homolog 2 (EZH2), a catalytic component of polycomb repressive complex 2 (PRC2), is commonly overexpressed or mutated in many cancer types, both of hematological and solid nature. Till now, plenty of EZH2 small molecule inhibitors have been developed and some of them have already been tested in clinical trials. Most of these inhibitors, however, are effective only in limited cases in the context of EZH2 gain-of-function mutated tumors such as lymphomas. Other cancer types with aberrant EZH2 expression and function require alternative approaches for successful treatment. One possibility is to exploit synthetic lethal strategy, which is based on the phenomenon that concurrent loss of two genes is detrimental but the deletion of either of them leaves cell viable. In the context of EZH2/PRC2, the most promising synthetic lethal target seems to be SWItch/Sucrose Non-Fermentable chromatin remodeling complex (SWI/SNF), which is known to counteract PRC2 functions. SWI/SNF is heavily involved in carcinogenesis and its subunits have been found mutated in approximately 20% of tumors of different kinds. In the current review, we summarize the existing knowledge of synthetic lethal relationships between EZH2/PRC2 and components of the SWI/SNF complex and discuss in detail the potential application of existing EZH2 inhibitors in cancer patients harboring mutations in SWI/SNF proteins. We also highlight recent discoveries of EZH2 involvement in tumor microenvironment regulation and consequences for future therapies. Although clinical studies are limited, the fundamental research might help to understand which patients are most likely to benefit from therapies using EZH2 inhibitors.

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Interdependence of PRC1 and PRC2 for recruitment to Polycomb Response Elements

Cited by 89 publications

References 86 publications

From Flies to Mice: The Emerging Role of Non-Canonical PRC1 Members in Mammalian Development

From Flies to Mice: The Emerging Role of Non-Canonical PRC1 Members in Mammalian Development

Drosophila DNA-Binding Proteins in Polycomb Repression

Potential of enhancer of zeste homolog 2 inhibitors for the treatment of SWI/SNF mutant cancers and tumor microenvironment modulation

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